title: Structural and biochemical studies of SLIP1-SLBP identify DBP5 and eIF3g as SLIP1-binding proteins.
abstract: In metazoans, replication-dependent histone mRNAs end in a stem-loop structure instead of the poly(A) tail characteristic of all other mature mRNAs. This specialized 3' end is bound by stem-loop binding protein (SLBP), a protein that participates in the nuclear export and translation of histone mRNAs. The translational activity of SLBP is mediated by interaction with SLIP1, a middle domain of initiation factor 4G (MIF4G)-like protein that connects to translation initiation. We determined the 2.5 Å resolution crystal structure of zebrafish SLIP1 bound to the translation-activation domain of SLBP and identified the determinants of the recognition. We discovered a SLIP1-binding motif (SBM) in two additional proteins: the translation initiation factor eIF3g and the mRNA-export factor DBP5. We confirmed the binding of SLIP1 to DBP5 and eIF3g by pull-down assays and determined the 3.25 Å resolution structure of SLIP1 bound to the DBP5 SBM. The SBM-binding and homodimerization residues of SLIP1 are conserved in the MIF4G domain of CBP80/20-dependent translation initiation factor (CTIF). The results suggest how the SLIP1 homodimer or a SLIP1-CTIF heterodimer can function as platforms to bridge SLBP with SBM-containing proteins involved in different steps of mRNA metabolism.
authors.affiliation: Structural Cell Biology Department, Max Planck Institute of Biochemistry, Munich, D-82152 Germany and Program in Molecular Biology and Biotechnology, University of North Carolina, Chapel Hill, NC 27599, USA.
authors.forename: Holger
authors.initials: H
authors.lastname: von Moeller
authors.forename: Rachel
authors.initials: R
authors.lastname: Lerner
authors.forename: Adele
authors.initials: A
authors.lastname: Ricciardi
authors.forename: Claire
authors.initials: C
authors.lastname: Basquin
authors.forename: William F
authors.initials: WF
authors.lastname: Marzluff
authors.forename: Elena
authors.initials: E
authors.lastname: Conti
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D053487:DEAD-box RNA Helicases / Q000737:chemistry* / Q000378:metabolism; D039621:Eukaryotic Initiation Factor-3 / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D029543:Nucleocytoplasmic Transport Proteins / Q000737:chemistry* / Q000378:metabolism; D054730:Protein Interaction Domains and Motifs; D055503:Protein Multimerization; D016601:RNA-Binding Proteins / Q000737:chemistry* / Q000378:metabolism; D016415:Sequence Alignment; D029961:Zebrafish Proteins / Q000737:chemistry* / Q000378:metabolism
chemical_list: D039621:Eukaryotic Initiation Factor-3; D029543:Nucleocytoplasmic Transport Proteins; D016601:RNA-Binding Proteins; C584140:SLBP protein, zebrafish; D029961:Zebrafish Proteins; C121148:DDX19B protein, human; D053487:DEAD-box RNA Helicases